Improving prediction of type 1 diabetes by testing non-HLA genetic variants in addition to HLA markers

Objective: The purpose of this study was to explore whether non-human leukocyte antigen (non-HLA) genetic markers can improve type 1 diabetes (T1D) prediction in a prospective cohort with high-risk HLA-DR, DQ genotypes.Methods: The Diabetes Autoimmunity Study in the Young (DAISY) follows prospectively for the development of T1D and islet autoimmunity (IA) children at increased genetic risk. A total of 1709 non-Hispanic White DAISY participants have been genotyped for 27 non-HLA single nucleotide polymorphisms (SNPs) and one microsatellite.Results: In multivariate analyses adjusting for family history and HLA-DR3/4 genotype, PTPN22 (rs2476601) and two UBASH3A (rs11203203 and rs9976767) SNPs were associated with development of IA [hazard ratio (HR) = 1.87, 1.55, and 1.54, respectively, all pConclusion: Addition of PTPN22 and UBASH3A SNPs to HLA-DR, DQ genotyping can improve T1D risk prediction.